Olestra
Nat Cooper

Chemical Concepts
Fats play a significant and unique role in bodily function.

We will see how researchers used these simple chemical concepts to invent and develop olestra and we will use these principles ourselves to evaluate and decide on nutritional issues

Micro/Macro
and Symbolic
Representation

It is perhaps revealing to think about the four steps of digestion:

1. Secretion
2. Emulsification
3. Hydrolysis
4. Transport

as processes that occur both in the stomach as a chemical reactor, and as the molecule-by-molecule processes these steps outline.

Here is your chance to think like a researcher. Read the text below then click on the quiz that will ask you to predict what the "very unexpected results" were.

What happens to the fats in our body once we consume them in food?

Lipid Metabolism
Original Results of the Mattson Volenhein Research
Fat Oxidation

Lipid Metabolism

Digestion converts the foods we eat to a form that the body can use for energy or store for future needs as fat.  Digestion is a catalyzed process - chemical reactions take place in the body that would not occur without the presence of catalysts called enzymes.  The specific enzymes that operate to catalyze fat digestion are called lipases.

When we enjoy a typical Western diet for a day we may consume on the order of 30 to 40 percent fat. These dietary lipids often include as much as 100 grams of triglycerides such as tristearin, a much smaller amount (4-8grams) of phospholipids, 0.4- 0.5 grams of cholesterol, the fat soluble vitamins A, D, E, and K, and small amounts of waxes from plant and animal cell walls. As we consume these wonderful foods the digestion process begins in the stomach and can be thought of as four major events:

1. the secretion of bile and the various lipases into the stomach (lipid breaking enzymes),
2. the emulsification or mixing of the lipids and the water soluble lipases and bile phases,
3. the enzymatic hydrolysis of the ester linkages in the triglycerides,
4. the formation of lipid containing bile salt micelles which transport the lipids to the cells for resynthesis or oxidation.

We will focus on the hydrolysis of the ester linkages, as this step is crucial for both the digestion of the typical dietary triesters and the lack of digestion for the hexa-, hepta-, and octa-esters that make up Olestra.

The lipases come from three sources: they are found in our food, excreted from our tongues (lingual) and produced in our pancreas. When they mix with our food they combine with a polypeptide, colipase that helps reduce the surface tension at the oil-water interface and helps assist the hydrolysis process. The lipases can then cleave the fatty acids from the glycerol molecule. While some lipases are non specific and can cleave all of the three fatty acids the primary process is controlled by the pancreatic lipase which is specific and cleaves only the first and third fatty acids, leaving a 2 monoglyceride intact.  The chemical equation looks like this:

   + 2H₂O    -->  2HO(O=C)C₁₇H₃₅   + 

Mattson and Volpenhein Research: The discoveries that two different enzymes control the hydrolysis or breaking of the ester linkage between the fatty acid and the glycerol molecule were part of the same studies that led to the development of Olestra. The Procter and Gamble research scientists, Fred Mattson and Robert Volpenhein first studied this triglyceride hydrolysis process in detail and then they continued this study with molecules that contained from one to eight alcohol/fatty acid bridges rather than the three that exist in triglycerides. This led to some very unexpected results which are discussed in the Olestra section of this ChemCases.com unit.

After this hydrolysis, there are several different pathways that the fats can follow. Most of the fatty acids and monoglycerides are recycled in the enterocyte. After this synthesis these new fats leave the cell in lipoprotein bundles known as chylomicrons and the various cholesterol carrying lipoproteins.

All of these lipoproteins contain a variety of cell targeting proteins that signal different destinations for the different lipoproteins. Most of this recycling effort is spent on fats that we do not burn for calories, but rather fats that function as cellular membranes, hormones such as cholesterol, and the many other lipid functions such as storage for energy.

Fat Oxidation:   Fats are also oxidized and provide us with the energy we fuel our bodies with. This oxidation process, known as Beta-oxidation is the process by which the long fatty acid chains are broken down into two carbon units and the energy provider, ATP.

The initial discovery that this oxidation process took place between the second (beta) and first (alpha) carbon, also represents a landmark event in biochemistry. In 1904 Franz Knoop made this discovery by attaching a synthetic label (a phenyl group) to the end of the fatty acid chain and then comparing the products, depending on whether an even or odd number carbon chain fatty acid had been used. While this experiment proved that the carbon chains were oxidized in two carbon units, the lasting significance is that this represented the first use of a synthetic label to figure out the reaction mechanism details. The use of other labels, including deuterium and radioisotopes, such as carbon-14, did not occur until several decades later.

So you have learned a little about how fats are metabolized and recycled in our bodies. Return to the Olestra Concept Map now and look at how this knowledge was used and expanded in the development of Olestra